This invention relates to the use of rapamycin prodrugs as immunosuppressant agents, e.g. for use in a human host in the treatment of autoimmune diseases and/or prevention of organ transplant rejections, intermediates formed in the preparation of the prodrugs as well as the prodrugs themselves.
In 1983, the United States Food and Drug Administration licensed cyclosporin A, an anti-rejection drug that revolutionized the field of organ transplant surgery. The drug acts by inhibiting the body's immune system from mobilizing its vast arsenal of natural protecting agents to reject the transplant's foreign protein. Although cyclosporin A is effective in fighting transplantation rejection, it suffers drawbacks in causing kidney failure, liver damage, and ulcers which in many cases can be very severe. Newer, safer drugs exhibiting less side effects are constantly being searched for.
Rapamycin has been found to be useful as an antifungal agent, U.S. Pat. No. 3,929,992, as well as capable of inhibition of the immune response, Martel, et al., Can. J, Physiol. Pharmacol., 55, 48-51 (1977).